Transferred entry: phosphatidylcholine desaturase. Now EC, microsomal oleoyl-lipid 12-desaturase
[EC created 1984, deleted 2015]
Transferred entry: long-chain acyl-CoA ω-monooxygenase. Now EC, long-chain acyl-CoA ω-monooxygenase
[EC created 2015, deleted 2018]
Accepted name: long-chain acyl-CoA ω-monooxygenase
Reaction: (1) oleoyl-CoA + [reduced NADPH—hemoprotein reductase] + O2 = 18-hydroxyoleoyl-CoA + [oxidized NADPH—hemoprotein reductase] + H2O
(2) linoleoyl-CoA + [reduced NADPH—hemoprotein reductase] + O2 = 18-hydroxylinoleoyl-CoA + [oxidized NADPH—hemoprotein reductase] + H2O
Other name(s): long-chain acyl-CoA ω-hydroxylase; CYP86A22 (gene name)
Systematic name: long-chain acyl-CoA,[reduced NADPH—hemoprotein reductase]:oxygen oxidoreductase (ω-hydroxylating)
Comments: A cytochrome P-450 (heme-thiolate) protein. The enzymes from solanaceous plants are involved in the biosynthesis of stigmatic estolide, a lipid-based polyester that forms a major component of the exudate.
1.  Han, J., Clement, J.M., Li, J., King, A., Ng, S. and Jaworski, J.G. The cytochrome P450 CYP86A22 is a fatty acyl-CoA ω-hydroxylase essential for estolide synthesis in the stigma of Petunia hybrida. J. Biol. Chem. 285 (2010) 3986–3996. [PMID: 19940120]
[EC created 2015 as EC, transferred 2018 to EC]
Accepted name: stearoyl-CoA 9-desaturase
Reaction: stearoyl-CoA + 2 ferrocytochrome b5 + O2 + 2 H+ = oleoyl-CoA + 2 ferricytochrome b5 + 2 H2O
Other name(s): Δ9-desaturase; acyl-CoA desaturase; fatty acid desaturase; stearoyl-CoA, hydrogen-donor:oxygen oxidoreductase
Systematic name: stearoyl-CoA,ferrocytochrome-b5:oxygen oxidoreductase (9,10-dehydrogenating)
Comments: An iron protein. The rat liver enzyme is an enzyme system involving cytochrome b5 and EC, cytochrome-b5 reductase. The ferricytochrome b5 produced is reduced by NADH and cytochrome-b5 reductase (EC
1.  Fulco, A.J. and Bloch, K. Cofactor requirements for the formation of Δ9-unsaturated fatty acids in Mycobacterium phlei. J. Biol. Chem. 239 (1964) 993–997. [PMID: 14167617]
2.  Oshino, N., Imai, Y. and Sato, R. Electron-transfer mechanism associated with fatty acid desaturation catalyzed by liver microsomes. Biochim. Biophys. Acta 128 (1966) 13–27. [PMID: 4382040]
3.  Oshino, N., Imai, Y. and Sato, R. A function of cytochrome b5 in fatty acid desaturation by rat liver microsomes. J. Biochem. (Tokyo) 69 (1971) 155–167. [PMID: 5543646]
4.  Strittmatter, P., Sputz, L., Corcoran, D., Rogers, M.J., Setlow, B. and Redline, R. Purification and properties of rat liver microsomal stearyl coenzyme A desaturase. Proc. Natl. Acad. Sci. USA 71 (1974) 4565–4569. [PMID: 4373719]
[EC created 1972 as EC, modified 1986, modified 2000, transferred 2000 to EC, modified 2003]
Accepted name: acyl-CoA 6-desaturase
Reaction: (1) linoleoyl-CoA + 2 ferrocytochrome b5 + O2 + 2 H+ = γ-linolenoyl-CoA + 2 ferricytochrome b5 + 2 H2O
(2) α-linolenoyl-CoA + 2 ferrocytochrome b5 + O2 + 2 H+ = stearidonoyl-CoA + 2 ferricytochrome b5 + 2 H2O
Other name(s): Δ6-desaturase; Δ6-fatty acyl-CoA desaturase; Δ6-acyl CoA desaturase; fatty acid Δ6-desaturase; fatty acid 6-desaturase; linoleate desaturase; linoleic desaturase; linoleic acid desaturase; linoleoyl CoA desaturase; linoleoyl-coenzyme A desaturase; long-chain fatty acid Δ6-desaturase; linoleoyl-CoA,hydrogen-donor:oxygen oxidoreductase; linoleoyl-CoA desaturase; FADS2 (gene name)
Systematic name: acyl-CoA,ferrocytochrome b5:oxygen oxidoreductase (6,7 cis-dehydrogenating)
Comments: An iron protein. The enzyme introduces a cis double bond at carbon 6 of acyl-CoAs. It is a front-end desaturase, introducing the new double bond between a pre-existing double bond and the carboxyl-end of the fatty acid. The human enzyme has a broad substrate range. It also acts on palmitoyl-CoA, generating sapienoyl-CoA [4], and on (9Z,12Z,15Z,18Z,21Z)-tetracosa-9,12,15,18,21-pentaenoyl-CoA, converting it to (6Z,9Z,12Z,15Z,18Z,21Z)-tetracosa-6,9,12,15,18,21-hexaenoyl-CoA as part of a pathway that produces docosahexaenoate [3]. The enzyme contains a cytochrome b5 domain that is assumed to act in vivo as the electron donor to the active site of the desaturase.
1.  Okayasu, T., Nagao, M., Ishibashi, T. and Imai, Y. Purification and partial characterization of linoleoyl-CoA desaturase from rat liver microsomes. Arch. Biochem. Biophys. 206 (1981) 21–28. [PMID: 7212717]
2.  Cho, H.P., Nakamura, M.T. and Clarke, S.D. Cloning, expression, and nutritional regulation of the mammalian Δ-6 desaturase. J. Biol. Chem. 274 (1999) 471–477. [PMID: 9867867]
3.  Sprecher, H. Metabolism of highly unsaturated n-3 and n-6 fatty acids. Biochim. Biophys. Acta 1486 (2000) 219–231. [PMID: 10903473]
4.  Ge, L., Gordon, J.S., Hsuan, C., Stenn, K. and Prouty, S.M. Identification of the Δ-6 desaturase of human sebaceous glands: expression and enzyme activity. J. Invest. Dermatol. 120 (2003) 707–714. [PMID: 12713571]
5.  Domergue, F., Abbadi, A., Zähringer, U., Moreau, H. and Heinz, E. In vivo characterization of the first acyl-CoA Δ6-desaturase from a member of the plant kingdom, the microalga Ostreococcus tauri. Biochem. J. 389 (2005) 483–490. [PMID: 15769252]
[EC created 1986 as EC, transferred 2000 to EC, modified 2015]
Accepted name: acyl-CoA (9+3)-desaturase
Reaction: (1) oleoyl-CoA + 2 ferrocytochrome b5 + O2 + 2 H+ = linoleoyl-CoA + 2 ferricytochrome b5 + 2 H2O
(2) palmitoleoyl-CoA + 2 ferrocytochrome b5 + O2 + 2 H+ = (9Z,12Z)-hexadeca-9,12-dienoyl-CoA + 2 ferricytochrome b5 + 2 H2O
Glossary: oleoyl-CoA = cis-octadec-9-enoyl-CoA = (9Z)-octadec-9-enoyl-CoA = 18:1 cis-9 = 18:1(n-9)
linoleoyl-CoA = cis,cis-octadeca-9,12-dienoyl-CoA = (9Z,12Z)-octadeca-9,12-dienoyl-CoA = 18:2(n-6)
palmitoleoyl-CoA = (9Z)-hexadec-9-enoyl-CoA
Other name(s): oleoyl-CoA 12-desaturase; Δ12 fatty acid desaturase; Δ126)-desaturase; oleoyl-CoA Δ12 desaturase; Δ12 desaturase; Δ12-desaturase; Δ12-fatty-acid desaturase; acyl-CoA,hydrogen donor:oxygen Δ12-oxidoreductase
Systematic name: acyl-CoA,ferrocytochrome b5:oxygen oxidoreductase (12,13 cis-dehydrogenating)
Comments: This microsomal enzyme introduces a cis double bond at position 12 of fatty-acyl-CoAs that contain a cis double bond at position 9. When acting on 19:1Δ10 fatty acyl-CoA the enzyme from the pathogenic protozoan Trypanosoma brucei introduces the new double bond at position 13, indicating that the new double bond is introduced three carbons from the existing cis double bond, towards the methyl-end of the fatty acid. Requires cytochrome b5 as the electron donor [4].
1.  Borgeson, C.E., de Renobales, M. and Blomquist, G.J. Characterization of the Δ12 desaturase in the American cockroach, Periplaneta americana: the nature of the substrate. Biochim. Biophys. Acta 1047 (1990) 135–140. [PMID: 2248971]
2.  Lomascolo, A., Dubreucq, E. and Galzy, P. Study of the Δ12-desaturase system of Lipomyces starkeyi. Lipids 31 (1996) 253–259. [PMID: 8900454]
3.  Tocher, D.R., Leaver, M.J. and Hodgson, P.A. Recent advances in the biochemistry and molecular biology of fatty acyl desaturases. Prog. Lipid Res. 37 (1998) 73–117. [PMID: 9829122]
4.  Petrini, G.A., Altabe, S.G. and Uttaro, A.D. Trypanosoma brucei oleate desaturase may use a cytochrome b5-like domain in another desaturase as an electron donor. Eur. J. Biochem. 271 (2004) 1079–1086. [PMID: 15009186]
[EC created 2008, modified 2015]
Accepted name: acyl-lipid ω-6 desaturase (cytochrome b5)
Reaction: an oleoyl-[glycerolipid] + 2 ferrocytochrome b5 + O2 + 2 H+ = a linoleoyl-[glycerolipid] + 2 ferricytochrome b5 + 2 H2O
Other name(s): oleate desaturase (ambiguous); linoleate synthase (ambiguous); oleoyl-CoA desaturase (incorrect); oleoylphosphatidylcholine desaturase (ambiguous); phosphatidylcholine desaturase (ambiguous); n-6 desaturase (ambiguous); FAD2 (gene name)
Systematic name: 1-acyl-2-oleoyl-sn-glycero-3-phosphocholine,ferrocytochrome-b5:oxygen oxidoreductase (12,13 cis-dehydrogenating)
Comments: This microsomal enzyme introduces a cis double bond in fatty acids attached to lipid molecules at a location 6 carbons away from the methyl end of the fatty acid. The distance from the carboxylic acid end of the molecule does not affect the location of the new double bond. The most common substrates are oleoyl groups attached to either the sn-1 or sn-2 position of the glycerol backbone in phosphatidylcholine. cf. EC, acyl-lipid ω-6 desaturase (ferredoxin).
1.  Pugh, E.L. and Kates, M. Characterization of a membrane-bound phospholipid desaturase system of Candida lipolytica. Biochim. Biophys. Acta 380 (1975) 442–453. [PMID: 166662]
2.  Slack, C.R., Roughan, P.G. and Browse, J. Evidence for an oleoyl phosphatidylcholine desaturase in microsomal preparations from cotyledons of safflower (Carthamus tinctorius) seed. Biochem. J. 179 (1979) 649–656. [PMID: 475773]
3.  Stymne, S. and Appelqvist, L.-A. The biosynthesis of linoleate from oleoyl-CoA via oleoyl-phosphatidylcholine in microsomes of developing safflower seeds. Eur. J. Biochem. 90 (1978) 223–229. [PMID: 710426]
4.  Smith, M.A., Cross, A.R., Jones, O.T., Griffiths, W.T., Stymne, S. and Stobart, K. Electron-transport components of the 1-acyl-2-oleoyl-sn-glycero-3-phosphocholine Δ12-desaturase (Δ12-desaturase) in microsomal preparations from developing safflower (Carthamus tinctorius L.) cotyledons. Biochem. J. 272 (1990) 23–29. [PMID: 2264826]
5.  Kearns, E.V., Hugly, S. and Somerville, C.R. The role of cytochrome b5 in Δ12 desaturation of oleic acid by microsomes of safflower (Carthamus tinctorius L.). Arch. Biochem. Biophys. 284 (1991) 431–436. [PMID: 1989527]
6.  Miquel, M. and Browse, J. Arabidopsis mutants deficient in polyunsaturated fatty acid synthesis. Biochemical and genetic characterization of a plant oleoyl-phosphatidylcholine desaturase. J. Biol. Chem. 267 (1992) 1502–1509. [PMID: 1730697]
[EC created 1984 as EC, transferred 2015 to EC]
Accepted name: acyl-lipid (n+3)-(Z)-desaturase (ferredoxin)
Reaction: an oleoyl-[glycerolipid] + 2 reduced ferredoxin [iron-sulfur] cluster + O2 + 2 H+ = a linoleoyl-[glycerolipid] + 2 oxidized ferredoxin [iron-sulfur] cluster + 2 H2O
Other name(s): acyl-lipid ω6-desaturase (ferredoxin); oleate desaturase (ambiguous); linoleate synthase (ambiguous); oleoyl-CoA desaturase (ambiguous); oleoylphosphatidylcholine desaturase (ambiguous); phosphatidylcholine desaturase (ambiguous); FAD6 (gene name)
Systematic name: oleoyl-[glycerolipid],ferredoxin:oxygen oxidoreductase (12,13 cis-dehydrogenating)
Comments: This plastidial enzyme is able to insert a cis double bond in monounsaturated fatty acids incorporated into glycerolipids. The enzyme introduces the new bond at a position 3 carbons away from the existing double bond, towards the methyl end of the fatty acid. The native substrates are oleoyl (18:1 Δ9) and (Z)-hexadec-7-enoyl (16:1 Δ7) groups attached to either position of the glycerol backbone in glycerolipids, resulting in the introduction of the second double bond at positions 12 and 10, respectively This prompted the suggestion that this is an ω6 desaturase. However, when acting on palmitoleoyl groups(16:1 Δ9), the enzyme introduces the second double bond at position 12 (ω4), indicating it is an (n+3) desaturase [3]. cf. EC, acyl-lipid (9+3)-(E)-desaturase.
1.  Schmidt, H. and Heinz, E. Desaturation of oleoyl groups in envelope membranes from spinach chloroplasts. Proc. Natl. Acad. Sci. USA 87 (1990) 9477–9480. [PMID: 11607123]
2.  Schmidt, H. and Heinz, E. Involvement of ferredoxin in desaturation of lipid-bound oleate in chloroplasts. Plant Physiol. 94 (1990) 214–220. [PMID: 16667689]
3.  Hitz, W.D., Carlson, T.J., Booth, J.R., Jr., Kinney, A.J., Stecca, K.L. and Yadav, N.S. Cloning of a higher-plant plastid ω-6 fatty acid desaturase cDNA and its expression in a cyanobacterium. Plant Physiol. 105 (1994) 635–641. [PMID: 8066133]
4.  Falcone, D.L., Gibson, S., Lemieux, B. and Somerville, C. Identification of a gene that complements an Arabidopsis mutant deficient in chloroplast ω 6 desaturase activity. Plant Physiol. 106 (1994) 1453–1459. [PMID: 7846158]
5.  Schmidt, H., Dresselhaus, T., Buck, F. and Heinz, E. Purification and PCR-based cDNA cloning of a plastidial n-6 desaturase. Plant Mol. Biol. 26 (1994) 631–642. [PMID: 7948918]
[EC created 2015]
Transferred entry: linoleoyl-CoA desaturase. Now EC, linoleoyl-CoA desaturase
[EC created 1986, deleted 2000]
Accepted name: 1-alkyl-2-acetylglycerol O-acyltransferase
Reaction: acyl-CoA + 1-O-alkyl-2-acetyl-sn-glycerol = CoA + 1-O-alkyl-2-acetyl-3-acyl-sn-glycerol
Other name(s): 1-hexadecyl-2-acetylglycerol acyltransferase
Systematic name: acyl-CoA:1-O-alkyl-2-acetyl-sn-glycerol O-acyltransferase
Comments: A number of acyl-CoAs can act as acyl donor; maximum activity is obtained with linoleoyl-CoA. Not identical with EC diacylglycerol O-acyltransferase.
1.  Kawasaki, T. and Snyder, F. Synthesis of a novel acetylated neutral lipid related to platelet-activating factor by acyl-CoA:1-O-alkyl-2-acetyl-sn-glycerol acyltransferase in HL-60 cells. J. Biol. Chem. 263 (1988) 2593–2596. [PMID: 3422635]
[EC created 1990]
Accepted name: very-long-chain 3-oxoacyl-CoA synthase
Reaction: a very-long-chain acyl-CoA + malonyl-CoA = a very-long-chain 3-oxoacyl-CoA + CO2 + CoA
Glossary: a very-long-chain acyl-CoA = an acyl-CoA thioester where the acyl chain contains 23 or more carbon atoms.
Other name(s): very-long-chain 3-ketoacyl-CoA synthase; very-long-chain β-ketoacyl-CoA synthase; condensing enzyme (ambiguous); CUT1 (gene name); CER6 (gene name); FAE1 (gene name); KCS (gene name); ELO (gene name)
Systematic name: malonyl-CoA:very-long-chain acyl-CoA malonyltransferase (decarboxylating and thioester-hydrolysing)
Comments: This is the first component of the elongase, a microsomal protein complex responsible for extending palmitoyl-CoA and stearoyl-CoA (and modified forms thereof) to very-long-chain acyl CoAs. Multiple forms exist with differing preferences for the substrate, and thus the specific form expressed determines the local composition of very-long-chain fatty acids [6,7]. For example, the FAE1 form from the plant Arabidopsis thaliana accepts only 16 and 18 carbon substrates, with oleoyl-CoA (18:1) being the preferred substrate [5], while CER6 from the same plant prefers substrates with chain length of C22 to C32 [4,8]. cf. EC, very-long-chain 3-oxoacyl-CoA reductase, EC, very-long-chain (3R)-3-hydroxyacyl-[acyl-carrier protein] dehydratase, and EC, very-long-chain enoyl-CoA reductase
1.  Toke, D.A. and Martin, C.E. Isolation and characterization of a gene affecting fatty acid elongation in Saccharomyces cerevisiae. J. Biol. Chem. 271 (1996) 18413–18422. [PMID: 8702485]
2.  Oh, C.S., Toke, D.A., Mandala, S. and Martin, C.E. ELO2 and ELO3, homologues of the Saccharomyces cerevisiae ELO1 gene, function in fatty acid elongation and are required for sphingolipid formation. J. Biol. Chem. 272 (1997) 17376–17384. [PMID: 9211877]
3.  Dittrich, F., Zajonc, D., Huhne, K., Hoja, U., Ekici, A., Greiner, E., Klein, H., Hofmann, J., Bessoule, J.J., Sperling, P. and Schweizer, E. Fatty acid elongation in yeast--biochemical characteristics of the enzyme system and isolation of elongation-defective mutants. Eur. J. Biochem. 252 (1998) 477–485. [PMID: 9546663]
4.  Millar, A.A., Clemens, S., Zachgo, S., Giblin, E.M., Taylor, D.C. and Kunst, L. CUT1, an Arabidopsis gene required for cuticular wax biosynthesis and pollen fertility, encodes a very-long-chain fatty acid condensing enzyme. Plant Cell 11 (1999) 825–838. [PMID: 10330468]
5.  Ghanevati, M. and Jaworski, J.G. Engineering and mechanistic studies of the Arabidopsis FAE1 β-ketoacyl-CoA synthase, FAE1 KCS. Eur. J. Biochem. 269 (2002) 3531–3539. [PMID: 12135493]
6.  Blacklock, B.J. and Jaworski, J.G. Substrate specificity of Arabidopsis 3-ketoacyl-CoA synthases. Biochem. Biophys. Res. Commun. 346 (2006) 583–590. [PMID: 16765910]
7.  Denic, V. and Weissman, J.S. A molecular caliper mechanism for determining very long-chain fatty acid length. Cell 130 (2007) 663–677. [PMID: 17719544]
8.  Tresch, S., Heilmann, M., Christiansen, N., Looser, R. and Grossmann, K. Inhibition of saturated very-long-chain fatty acid biosynthesis by mefluidide and perfluidone, selective inhibitors of 3-ketoacyl-CoA synthases. Phytochemistry 76 (2012) 162–171. [PMID: 22284369]
[EC created 2012]
Accepted name: long-chain-fatty-acid—CoA ligase
Reaction: ATP + a long-chain fatty acid + CoA = AMP + diphosphate + an acyl-CoA
Glossary: a long-chain-fatty acid = a fatty acid with an aliphatic chain of 13-22 carbons.
Other name(s): acyl-CoA synthetase; fatty acid thiokinase (long chain); acyl-activating enzyme; palmitoyl-CoA synthase; lignoceroyl-CoA synthase; arachidonyl-CoA synthetase; acyl coenzyme A synthetase; acyl-CoA ligase; palmitoyl coenzyme A synthetase; thiokinase; palmitoyl-CoA ligase; acyl-coenzyme A ligase; fatty acid CoA ligase; long-chain fatty acyl coenzyme A synthetase; oleoyl-CoA synthetase; stearoyl-CoA synthetase; long chain fatty acyl-CoA synthetase; long-chain acyl CoA synthetase; fatty acid elongase; LCFA synthetase; pristanoyl-CoA synthetase; ACS3; long-chain acyl-CoA synthetase I; long-chain acyl-CoA synthetase II; fatty acyl-coenzyme A synthetase; long-chain acyl-coenzyme A synthetase; FAA1
Systematic name: long-chain fatty acid:CoA ligase (AMP-forming)
Comments: Acts on a wide range of long-chain saturated and unsaturated fatty acids, but the enzymes from different tissues show some variation in specificity. The liver enzyme acts on acids from C6 to C20; that from brain shows high activity up to C24.
1.  Bakken, A.M. and Farstad, M. Identical subcellular distribution of palmitoyl-CoA and arachidonoyl-CoA synthetase activities in human blood platelets. Biochem. J. 261 (1989) 71–76. [PMID: 2528345]
2.  Hosaka, K., Mishima, M., Tanaka, T., Kamiryo, T. and Numa, S. Acyl-coenzyme-A synthetase I from Candida lipolytica. Purification, properties and immunochemical studies. Eur. J. Biochem. 93 (1979) 197–203. [PMID: 108099]
3.  Nagamatsu, K., Soeda, S., Mori, M. and Kishimoto, Y. Lignoceroyl-coenzyme A synthetase from developing rat brain: partial purification, characterization and comparison with palmitoyl-coenzyme A synthetase activity and liver enzyme. Biochim. Biophys. Acta 836 (1985) 80–88. [PMID: 3161545]
4.  Tanaka, T., Hosaka, K., Hoshimaru, M. and Numa, S. Purification and properties of long-chain acyl-coenzyme-A synthetase from rat liver. Eur. J. Biochem. 98 (1979) 165–172. [PMID: 467438]
[EC created 1961, modified 1989, modified 2011]